Chang Zhibo
Department of Thoracic Surgery, The Second Affiliated Hospital of Zhejiang University School of Medicine, Zhejiang, Hangzhou, 310009, China.
Cancer Cell Int. 2025 May 23;25(1):189. doi: 10.1186/s12935-025-03814-x.
Lung cancer (LC) is one of the most common malignant tumors globally. Non-SMC condensin II complex subunit D3 (NCAPD3) has been involved in the progression of many kinds of tumors. However, the effects of NCAPD3 in LC remain unclear. NCAPD3 expression was investigated by the Ualcan database and using Western blot. The effect of NCAPD3 on prognosis was explored via the Kaplan-Meier plotter database. Cell viability, colony formation, apoptosis, and Transwell assays, and in vivo tumorigenesis were performed to reveal the biological roles of NCAPD3. Glycolysis was assessed via measurement of glucose consumption, extracellular acidification rate (ECAR), lactate production, and ATP levels. The deeper mechanisms of NCAPD3 were investigated by Western blot and rescue experiments. Upregulation of NCAPD3 levels in LC tissues was found in Ualcan and significantly associated with poor prognosis. The expression of NCAPD3 was up-regulated in LC cell lines compared to BEAS-2B cells. Knockdown and overexpression experiments suggested that proliferation, apoptosis, migration, invasion, and glycolysis were regulated by NCAPD3 via the MEK/ERK/LDHA pathway. Additionally, NCAPD3 knockdown inhibited tumor growth in vivo. Mechanistically, NCAPD3 overexpression-mediated activation of the MEK/ERK/LDHA pathway and proliferation, Glucose uptake, and glycolysis were attenuated by MEK inhibitor U0126. Also, histone lactylation helps in tumorigenesis by promoting NCAPD3 expression. Taken together, our results revealed that histone lactylation of NCAPD3 promoted proliferation, migration, invasion, and glycolysis through modulating the MEK/ERK/LDHA signaling pathway in LC, which highlights a novel understanding of NCAPD3 in LC.
肺癌（LC）是全球最常见的恶性肿瘤之一。非SMC凝聚素II复合物亚基D3（NCAPD3）已参与多种肿瘤的进展。然而，NCAPD3在肺癌中的作用仍不清楚。通过Ualcan数据库和蛋白质免疫印迹法研究NCAPD3的表达。通过Kaplan-Meier绘图仪数据库探讨NCAPD3对预后的影响。进行细胞活力、集落形成、凋亡和Transwell实验以及体内肿瘤发生实验，以揭示NCAPD3的生物学作用。通过测量葡萄糖消耗、细胞外酸化率（ECAR）、乳酸生成和ATP水平来评估糖酵解。通过蛋白质免疫印迹法和拯救实验研究NCAPD3的深层机制。在Ualcan数据库中发现肺癌组织中NCAPD3水平上调，且与预后不良显著相关。与BEAS-2B细胞相比，NCAPD3在肺癌细胞系中的表达上调。敲低和过表达实验表明，NCAPD3通过MEK/ERK/LDHA途径调节增殖、凋亡、迁移、侵袭和糖酵解。此外，敲低NCAPD3可抑制体内肿瘤生长。机制上，NCAPD3过表达介导的MEK/ERK/LDHA途径激活以及增殖、葡萄糖摄取和糖酵解被MEK抑制剂U0126减弱。此外，组蛋白乳酸化通过促进NCAPD3表达有助于肿瘤发生。综上所述，我们的结果表明，NCAPD3的组蛋白乳酸化通过调节肺癌中的MEK/ERK/LDHA信号通路促进增殖、迁移、侵袭和糖酵解，这为肺癌中NCAPD3的研究提供了新的认识。
